Proteomic Analysis of Dacryoliths from Patients with or without Topical Rebamipide Treatment

Mano, Fukutaro; Takimoto, Hiroki; Oe, Masako; Chang, Kuo-Chung; Mano, Tomoo; Yoshida, Yutaka

doi:10.1159/000487585

Cited by 12 publications

(6 citation statements)

References 10 publications

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“…The first proteomic analysis of MPC-Ds (dacryoliths) in the context of rebamipide treatment was conducted in 2018 as well, identifying the proteins present in MPC-Ds [37]. Here, we link these findings to the localization of various antigens in the tissue, employing IF.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil Extracellular Traps Drive Dacryolithiasis

Zlatar,

Timm,

Lochnit

et al. 2023

Cells

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Mucopeptide concretions, previously called dacryoliths, are macroscopic stones that commonly obstruct the lacrimal sac. The mechanism behind dacryolithiasis remains unclear; however, the involvement of various immune cells, including neutrophils, has been confirmed. These findings remain limited, and no information on neutrophil extracellular traps (NETs), essentially involved in the pathogenesis of other lithiases, is available yet. Here, we employ microcomputed tomography, magnetic resonance tomography, histochemistry, mass spectrometry, and enzyme activity analyses to investigate the role of neutrophils and NETs in dacryolithiasis. We classify mucopeptide concretions into three types, with respect to the quantity of cellular and acellular material, polysaccharides, and mucosubstances. We propose the role of neutrophils and NETs within the existing model of gradual formation and growth of mucopeptide concretions, with neutrophils contributing to the initial stages of dacryolithiasis, as they localized on the inner (older) parts of the tissue. As NETs localized on the outer (newer) parts of the tissue, we link their role to the late stages of dacryolithiasis, presumably maintaining the proinflammatory environment and preventing efficient clearance. An abundance of IgG on the surface indicates the involvement of the adaptive immune system later as well. These findings bring new perspectives on dacryolithiasis, in which the innate and adaptive immune system are essentially involved.

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Section: Discussionmentioning

confidence: 99%

Neutrophil Extracellular Traps Drive Dacryolithiasis

Zlatar,

Timm,

Lochnit

et al. 2023

Cells

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“…Mass spectroscopic analysis of dacryoliths has revealed the presence of several proteins, including hemoglobin, albumin, lysozyme, S-100A8, S-100A9, cathepsin, neutrophil elastase (NE), neutrophil gelatinase-associated lipocalin, myeloperoxidase, lactotransferrin, and prolactin-inducible protein showing that most core proteins of dacryoliths are involved in immune and inflammatory responses. 21 These findings, when taken with electron microscopic features, provide new insights into the possible etiopathogenesis of dacryolith formation.…”

Section: Etiopathogenesis Of Dacryolithsmentioning

confidence: 90%

“…1,7,9–11 This review aims to elucidate and reconstruct the possible sequence of events in the etiopathogenesis of noninfectious dacryolithiasis, drawing primarily on basic science work carried out over the last decade by the authors’ group, but also by other groups. 5–30…”

mentioning

confidence: 99%

Dacryolithogenesis or Dacryolithiasis—The Story So Far

Ali,

Heichel,

Paulsen

2023

Ophthalmic Plastic &Amp; Reconstructive Surgery

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The term dacryoliths refers to the concretions found within the lacrimal system. When the term dacryoliths is unspecified, it usually refers to the noninfectious dacryoliths commonly isolated from the lacrimal sac and the nasolacrimal duct. More often, they are diagnosed incidentally during a dacryocystorhinostomy, and the reported incidence among all dacryocystorhinostomy surgeries is 5.7% to as high as 18%. Dacryolithiasis is a complex process occurring within the lacrimal system, and current evidence suggests a multifactorial etiology. The sequence of events can be summarized broadly into 4 stages: stage of susceptibility, stage of initiation/trigger, stage of development, and stage of maintenance. The triggering event is the breach of the lacrimal sac or nasolacrimal duct epithelium, resulting in microtrauma with blood leakage. The blood clots act as a nidus for subsequent sequential laying of mucopeptides, cellular debris present locally, debris washed from the ocular surface, and extraneous agents in tears. This process is aided by altered rheology and composition of the tear film. After the formation of dacryoliths, extracellular neutrophil traps usually form on the surface, which help to maintain the dacryoliths (which do not dissolve). This review highlights and discusses the possible sequence of events during dacryolithiasis.

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“…The content of dacryoliths was found to be organic material with minerals such as calcium and magnesium 14 . In addition, Mano et al reported that the protein pro les of dacryoliths were different between ROS and non-ROS group 15 . However, the exact composition of organic material is unclear in either with or without ROS application.…”

Section: Chemical Analysis Of Lacrimal Concretionsmentioning

confidence: 99%

Histochemical Analysis of Lacrimal Concretions in the Patients using Rebamipide Ophthalmic Suspension

Yamashita

Hiraoka

Sugita

et al. 2020

Preprint

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Backgroud: Concretions of the lacrimal drainage system can cause dacryocystitis. In the present study, our patient developed dacryocystisis with lacrimal concretions of a white soft mass. Rebamipide ophthalmic suspension had been applied for treatment of dry eye. To evaluate the pathogenic mechanism of the case, histological and chemical studies were performed.Case presentation: Our case was woman in her seventies. She had a medical history of rheumatoid arthritis. She was referred to our hospital for dacryocystitis after showing a poor response to treatment with antibiotic agents. A head computed tomography (CT) scan showed ductal high-density deposits along the lacrimal sacs. During dacryocystotomy, the hypertrophy of the lacrimal sacs was found replete with pus and cottage cheese-like white substances. The extracts were surgically removed and histological and chemical analysis was performed. The histological examination showed granulation tissues and acellular amorphous material with crystal-like structures. Positive staining by Alcian blue and Kossa was found in crystal-like legions. The extract obtained from the concretions showed the same fluorescence band and UV absorption spectrum in thin layer chromatography (TLC) and spectrometry, respectively, as rebamipide.Conclusion: Our findings suggest that the obstruction by lacrimal concretions containing rebamipide resulted in dacryocystitis in this case. In addition, it is speculated that in patients who have impaired tear secretion, refractory dacryocystitis may be evoked following the accumulation of rebamipide in the lacrimal sacs.

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Proteomic Analysis of Dacryoliths from Patients with or without Topical Rebamipide Treatment

Cited by 12 publications

References 10 publications

Neutrophil Extracellular Traps Drive Dacryolithiasis

Neutrophil Extracellular Traps Drive Dacryolithiasis

Dacryolithogenesis or Dacryolithiasis—The Story So Far

Histochemical Analysis of Lacrimal Concretions in the Patients using Rebamipide Ophthalmic Suspension

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